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PubMed2026

Spatial transcriptomics of Ciona adult brains reveals functional zonalization and insights into neural gland function.

The ascidian Ciona is a pivotal chordate model for illuminating the evolutionary origins of the vertebrate brain. Here, spatial transcriptomics of the adult Ciona neural complex, combined with image-based computational super-resolution mapping, resolved distinct tissue domains including the cerebral ganglion, neural gland, ciliated funnel, neural gland duct/dorsal strand, and body wall muscle. Within the cerebral ganglion, high-resolution mapping revealed clear molecular zonalization separating the cortex and medulla, alongside regional specialization within the cortex itself. The neural gland exhibited localized enrichment of genes associated with extracellular matrix and cell-cell interactions. These spatial features suggest that the neural gland functions as a homeostatic and signaling interface, reminiscent of primitive vertebrate meninges or choroid plexus. Overall, this spatially defined gene expression map provides a foundational framework for understanding functional regionalization in the tunicate brain and its evolutionary relationship to vertebrate nervous systems.

Ciona↗

PubMed2026

Triacylglycerol metabolism is a novel target to combat West Nile virus infection.

West Nile virus (WNV) is a zoonotic Orthoflavivirus transmitted by mosquitoes that is responsible for outbreaks of meningitis and encephalitis worldwide. Driven by climate change, WNV has expanded as a global public health concern, particularly in temperate regions. However, there are still no specific approved therapies, reinforcing the need for antiviral development. Previous works have documented that WNV multiplication strictly depends on certain cellular lipids. To identify novel lipid-related therapeutic targets, we analyzed the infection driven alterations in the CNS lipidome, the primary tissue supporting WNV replication. Our results indicated that the major alterations in the brain lipid content of WNV-infected mice corresponded to triacylglycerols (TAGs). Moreover, transcriptomic analysis showed that infected brains underwent changes in the expression of TAG metabolism. Supplementation with exogenous fatty acids increased lipid droplets (LD) content and promoted viral replication in cell culture models. On the contrary, pharmacological intervention in TAG metabolism using diacylglycerol acyltransferase inhibitors (DGATi) suppressed WNV multiplication in cell culture models. As a proof-of-concept of the therapeutic potential of DGATi, treatment of mice with A922500 reduced viral burden in the brain and proinflammatory cytokine production. Overall, our results unveil the importance of LDs and glycerolipid metabolism for WNV and highlight the potential of therapeutic interventions targeting this pathway to control viral replication and neuroinflammation.

West Nile virus; lipid↗

PubMed2026

Precision Oncology in Hepatopancreatobiliary Cancer Surgery.

Advances in technology have allowed for the characterization of tumors at the genomic, transcriptomic, and proteomic levels. There are well-established targets for biliary tract cancers, with exciting new targets emerging in pancreatic ductal adenocarcinoma and potential targets in hepatocellular carcinoma. Taken together, these data suggest an important role for molecular profiling for personalizing cancer therapy in advanced disease and need for design of novel neoadjuvant studies to leverage these novel therapeutics perioperatively in the surgical patient.

Humans↗

PubMed2026

[Specificity in the management of gynecological cancers in French overseas departments].

The five overseas departments and regions (DROMs) are Guadeloupe, French Guiana, Reunion, Martinique and Mayotte. In the DROMs, certain areas show significantly higher incidence rates for certain cancers, particularly gynaecological cancers; overall, the 5-year net standardised survival rates are lower than those observed in mainland France. Here, we present an overview of the management of gynaecological cancers in each DROM.

Humans↗

PubMed2026

Sodium-glucose cotransporter-2 inhibitors and gastrointestinal neoplasm risk in type 2 diabetes: a systematic review and meta-analysis of randomized controlled trials.

The potential carcinogenic effects of sodium-glucose cotransporter 2 (SGLT2) inhibitors in patients with type 2 diabetes mellitus (T2DM) remain controversial, particularly regarding site-specific gastrointestinal (GI) neoplasms. This systematic review and meta-analysis aimed to determine the relationship between SGLT2 inhibitors and the risk of GI neoplasms in patients with T2DM. We searched PubMed, EMBASE, Cochrane CENTRAL, Scopus, and Web of Science through March 17, 2025, for RCTs in T2DM comparing SGLT2 inhibitors with placebo or active comparators. Two reviewers independently screened studies, extracted data, and assessed the risk of bias. The primary outcome was GI neoplasms reported in publications, supplementary materials, or trial registries, usually as adverse events rather than centrally adjudicated cancer endpoints. Pooled odds ratios (ORs) with 95% confidence intervals (CIs) were calculated in Stata 17.0. In 48 RCTs (n = 48,765), SGLT2 inhibitor therapy was not associated with overall GI neoplasm risk (OR = 1.10, 95% CI: 0.84-1.44; p = 0.46; I² = 0%). Site-specific analyses showed no statistically significant association for esophageal (OR = 1.12, 95% CI 0.37-3.45), gastric (1.20, 0.65-2.23), hepatic (0.62, 0.31-1.22), pancreatic (0.91, 0.51-1.64), colonic (1.28, 0.78-2.08), colorectal (0.76, 0.27-2.17), and rectal neoplasms (0.98, 0.49-1.97), with all p-values > 0.05. Subgroup analyses by agents (e.g., canagliflozin, dapagliflozin, empagliflozin), baseline age, body mass index (BMI), HbA1c, treatment duration, and dose were also non-significant (all p > 0.05). Approximately half of the trials had follow-up of one year or less, limiting our ability to evaluate long-term risk. Available RCT evidence does not show a clear increase in GI neoplasm risk with SGLT2 inhibitors in T2DM. However, limited follow-up, low event counts, and non-cancer-specific outcome ascertainment, the findings should be interpreted as reassuring but not definitive evidence of long-term oncologic safety.Systematic review registration: PROSPERO No. CRD42024619019.

Humans↗

PubMed2026

Neoplasms in prune belly syndrome: A novel case of early-onset metastatic bladder carcinoma and systematic review of reported tumors.

PURPOSE: Prune Belly Syndrome (PBS) is a rare congenital malformation complex characterized by cryptorchidism, urinary tract abnormalities and deficiency of the abdominal wall musculature. Although advances in neonatal and reconstructive care have substantially improved survival, the long-term risk of malignancy in this population remains poorly defined. We report a novel case of early-onset metastatic bladder carcinoma in a patient with PBS and perform a systematic review of all tumors described in association with the syndrome. METHODS: A systematic literature review was performed according to PRISMA guidelines and registered in PROSPERO (CRD420251072086). Databases searched through April 2025 included PubMed, Embase, Web of Science, ClinicalTrials.gov, Cochrane, and SciELO. Reported tumor cases in PBS patients were identified and classified as either PBS-associated or not. We additionally describe a new case of invasive bladder carcinoma. RESULTS: Seventeen studies comprising 20 patients met inclusion criteria. Tumors directly related to the genitourinary tract accounted for half of the cases. Bladder carcinoma was the most frequent neoplasm (35%), followed by hepatoblastoma (25%). Bladder tumors occurred at markedly younger ages and often presented as advanced diseases. Our index case involved a 33-year-old man with PBS who developed metastatic muscle-invasive urothelial carcinoma and died shortly after diagnosis. DISCUSSION: Improved survival in PBS has led to recognition of new late complications, including malignancy. Tumorigenesis may be influenced by chronic urinary stasis, infection, catheterization, cryptorchidism, and underlying genitourinary developmental abnormalities. These findings should be interpreted as hypothesis-generating given the limited number of reported cases. CONCLUSION: Although uncommon, malignancies in PBS may occur earlier and behave more aggressively than in the general population. Given the current level of evidence, careful long-term follow-up with clinical awareness is warranted, rather than routine invasive screening for all patients.

Humans↗

PubMed2026

The Natural History of Residual and Recurrent Disease in Advanced Juvenile Nasopharyngeal Angiofibroma: A Systematic Review.

OBJECTIVE: This systematic review explores the natural history of residual and recurrent juvenile nasopharyngeal angiofibromas (JNAs) to inform clinical decision-making. DATA SOURCES: PubMed, Embase, Scopus, and Web of Science. REVIEW METHODS: A systematic literature review was conducted according to PRISMA guidelines across PubMed, Embase, Scopus, and Web of Science from inception to February 20, 2025 and was re-run on September 21, 2025. Studies included patients with advanced JNA and documented follow-up of residual or recurrent disease. Descriptive statistics, chi-squared analysis, and analysis of variance were used to evaluate treatment outcomes across different modalities including surgery, radiotherapy, gamma knife surgery, and medical therapies. RESULTS: Twenty-one studies encompassing 131 male patients (mean age 16.3 years) were included. Residual or recurrent disease demonstrated complete involution in 41%, stable disease in 29%, and reduction in size in 25% of cases. Only 2% of patients had progressive disease. A statistically significant association was observed between treatment modality and outcome (p = 0.015), with radiotherapy, either alone, or as part of a multimodal approach, showing the highest rates of spontaneous involution. CONCLUSION: Residual and recurrent JNAs often remain stable or regress without further intervention. Close surveillance with imaging is a safe and effective strategy for asymptomatic patients, minimizing the risks of additional treatment in a young patient population with disease near critical anatomical structures.

Humans↗

PubMed2026

Structural complexity and mechanistic diversity of MECOM rearrangements in myeloid neoplasms.

Rearrangements involving MECOM at chromosome 3q26.2 are recurrent in myeloid neoplasms, classically represented by inv(3)(q21q26.2) and t(3;3)(q21;q26.2), which reposition the GATA2-distal haematopoietic enhancer and drive aberrant EVI1 overexpression. However, the full structural and mechanistic diversity of MECOM rearrangements (MECOM-r) is yet to be explored. We retrospectively analysed 97 cases with cytogenetically defined MECOM-r and identified 12 with complex rearrangements using GTG-banded karyotyping and tri-colour interphase/metaphase fluorescence in situ hybridisation analyses. These 12 cases demonstrated remarkable structural heterogeneity. The abnormalities encompassed translocations, inversions, insertions, duplications, and deletions, which often coexisted within the same specimen as multiple rearranged subclones. Insertional events emerged as a distinct mechanism of MECOM activation. These encompassed insertions of MYNN and/or MECOM into chromosomes 1 and 6, insertion of chromosome 8 segment into MECOM, and inverted insertions between homologous chromosome 3 segments. Recurrent breakpoints at 3q21 across multiple cases, together with localised copy number imbalances frequently involving the MYNN and GOLIM4 loci at 3q26.2, underscore the architectural fragility of these two regions. Co-occurring abnormalities such as -5/del(5q), -7/del(7q), and TP53 loss were common, reflecting a permissive genomic background for chromosomal reassembly. Our findings expand the mechanistic landscape of MECOM-r beyond canonical inv(3)/t(3;3), establishing 3q21 and 3q26.2 as structural 'hotspots' and genomic instability hubs. Distinct from fusion-driven oncogenes such as KMT2A, MECOM activation results from enhancer hijacking and regional structural remodelling, leading to EVI1 overexpression and clonal evolution in myeloid malignancies.

Humans↗

PubMed2026

Clinical and genetic features of Ph-negative myeloproliferative neoplasms with dual-driver gene positivity.

OBJECTIVES: To investigate the clinical laboratory characteristics and gene mutation features of dual-driver gene positivity in patients with Philadelphia chromosome-negative myeloproliferative neoplasm (Ph-negative MPN). METHODS: We conducted a retrospective analysis of clinical data and genetic test results from 203 newly diagnosed patients with Ph-negative MPN. Of these, 194 had single-driver gene positivity and 9 had dual-driver gene positivity. High-throughput sequencing was used to detect mutations in JAK2, CALR, and MPL. Clinical characteristics and gene mutation profiles were compared between the two patient groups. RESULTS: The incidence of dual-driver gene positivity was 4.4% (9/203), with the most common combinations being JAK2 with CALR (4 patients) and JAK2 with MPL (4 patients). Compared with the single-driver group, the dual-driver group had a significantly higher risk of bleeding [4.1% (8/194) vs. 33.3% (3/9), P = 0.008] and a higher proportion of uncommon mutations [3.6% (7/194) vs. 33.3% (3/9), P = 0.006]. No statistically significant differences were observed between the two groups regarding age, thrombosis incidence, splenomegaly, or routine blood test indicators. During follow-up, 1 patient in the dual-driver group died from cerebrovascular disease. No leukaemia transformation or disease-related deaths occurred among the remaining patients. DISCUSSION: The increased bleeding risk in dual-driver patients may be related to a higher proportion of CALR mutations, elevated platelet counts, and higher variant allele frequencies, though these findings require validation in larger cohorts due to the small sample size. The higher prevalence of uncommon mutations suggests a more complex mutational landscape in this subgroup. CONCLUSION: Patients with Ph-negative MPN and dual-driver gene positivity may have a higher risk of bleeding and a more complex gene mutation profile.

Humans↗

PubMed2026

Adjuvant CDK4/6 inhibitors in early-stage breast cancer: Clinical evidence and considerations for risk stratification and treatment selection.

Hormone receptor-positive, human epidermal growth factor receptor 2-negative breast cancer is the most common biologic subtype and carries a persistent risk of recurrence, particularly in patients with high-risk, early-stage disease. Cyclin-dependent kinase 4 and 6 inhibitors, initially established as a standard component of first-line therapy in the metastatic setting based on improvements in progression-free and overall survival, have since been evaluated in the adjuvant setting. While adjuvant palbociclib did not improve invasive disease-free survival, the monarchE and NATALEE trials demonstrated that abemaciclib and ribociclib, respectively, reduce recurrence risk in patients with high-risk, early-stage disease, with emerging overall survival data further supporting their use. However, the absolute magnitude of benefit varies substantially with baseline risk, and treatment-related toxicity and adherence challenges must be considered, as approximately 20% to 25% of patients discontinue therapy before completion. The integration of these agents into clinical practice also intersects with ongoing efforts to deescalate axillary surgery, as treatment eligibility has been largely defined by anatomic staging, particularly nodal status. Available data suggest that the incremental impact of axillary surgery on identifying candidates for cyclin-dependent kinase 4 and 6 inhibition is modest, especially among the favorable-risk populations now eligible for surgical deescalation. As the field evolves, advances in molecular risk stratification, genomic profiling, and dynamic biomarkers are poised to shift treatment selection from anatomic staging toward biologically driven approaches. Multidisciplinary decision-making that integrates tumor biology, anticipated absolute benefit, toxicity, patient preferences, and surgical considerations will be essential to ensure individualized care.

Humans↗

PubMed2026

Frequent mutations in the BIRC3 gene promote metastatic potential of nasopharyngeal carcinoma cells through the TRAF2-NF-κB pathway.

Nasopharyngeal carcinoma (NPC) is a head and neck cancer characterized by highly locoregionally invasive behavior attributable to the latent infection with Epstein-Barr virus (EBV) and genomic instability. It is well established that EBV-encoded oncogenic molecules actively contribute to the malignant behavior of NPC cells. However, the mechanism by which aberrant genomic alterations enable NPC cells to become aggressive remains largely unknown. In the present study, whole-exome sequencing (WES) revealed that the gene encoding the baculoviral IAP repeat-containing 3 (BIRC3) protein was frequently mutated in circulating tumor cells (CTCs) but not in paired primary tumor cells from patients with metastatic NPC. A minigene assay indicated that the c.637 A > G mutation disrupted normal mRNA splicing, resulting in the partial deletion of Exons 2 and 3 and altered stability of BIRC3 mRNA. In vitro experiments demonstrated that ectopic expression of the BIRC3c.637A>G mutant enhanced NPC cell invasive properties, including proliferation, resistance to apoptosis, migration, and invasion. Furthermore, overexpression of wild-type BIRC3 promoted invasive characteristics in NPC cells through the TRAF2-NF-κB signaling axis. In summary, BIRC3 acts as a regulator of the malignant features of NPC cells. Frequent BIRC3 mutations in CTCs, such as the c.637 A > G mutation, further enhance the metastatic potential of disseminated NPC cells by inducing aberrant alternative splicing. These findings suggest the therapeutic feasibility of targeting the BIRC3/TRAF2/NF-κB axis in the treatment of NPC.

Humans↗

PubMed2026

Feasibility and Efficacy of Lorlatinib in Japanese Patients With Relapsed/Refractory ALK-Aberrant Neuroblastoma.

Lorlatinib, a third-generation ALK inhibitor, was administered off-label to five heavily pretreated patients with relapsed or refractory ALK-aberrant neuroblastoma. ALK alterations included F1174L, R1275Q, BEND5::ALK fusion, and ALK amplification; three patients had MYCN amplification. Best responses were three partial responses and two disease progressions. The longest progression-free survival (6.7 months) occurred in a patient with F1174L and non-amplified MYCN, whereas rapid progression was observed in two MYCN-amplified cases. Lorlatinib was generally well tolerated with manageable adverse events. These findings suggest that lorlatinib is a feasible therapeutic option in ALK-aberrant neuroblastoma and that clinical heterogeneity in treatment response warrants further investigation.

Humans↗

PubMed2026

Opposing kinase signaling may underlie the inverse relationship between cancer and Alzheimer's disease.

Cancer and Alzheimer's disease (AD) are leading causes of mortality and exhibit an inverse relationship, where AD patients have reduced cancer risk and vice versa. However, the molecular basis of this relationship remains poorly understood. We reanalyzed published proteomic and phosphoproteomic datasets to investigate this relationship. Differentially abundant proteins were identified in lung adenocarcinoma and glioblastoma samples relative to controls and compared with proteins altered in AD brains, revealing 37 proteins with opposing abundance patterns. Protein-protein interaction and pathway analyses revealed enrichment in kinase signaling and phosphorylation pathways. Phosphoproteomic analysis identified 52 differentially phosphorylated sites with opposing patterns, while kinase-substrate enrichment analysis identified 44 kinases with opposing inferred activity profiles. Integration of kinase activity and phosphosite data identified 29 kinase-phosphosite pairs, including 4 prioritized pairs with opposing patterns relevant to both diseases. Across seven independent cancer cohorts, 17 of 20 statistically significant phosphosite-cohort comparisons (85%) were concordant with the discovery findings, supporting reproducibility of the prioritized phosphosites. Together, these findings highlight opposing kinase signaling as a prominent feature of the inverse relationship and suggest potential biomarkers and therapeutic targets. This study provides a novel systems-level framework for investigating inverse relationships, supported by an R Shiny application for data exploration (https://advscancer.shinyapps.io/advscancer/). SIGNIFICANCE: This study presents an integrated proteomic and phosphoproteomic framework for investigating the inverse relationship between cancer and Alzheimer's disease (AD). By integrating differential protein abundance, phosphosite phosphorylation, inferred kinase activity, and curated kinase-substrate relationships, we identified opposing signaling patterns and prioritized four kinase-phosphosite pairs. Independent evaluation across seven CPTAC cancer cohorts supported the reproducibility of the prioritized phosphosite patterns. These findings provide insight into molecular processes potentially associated with the inverse relationship between cancer and AD, identify candidate biomarkers and therapeutic targets, and demonstrate the value of systems-level, data-driven approaches for investigating shared and opposing disease processes.

Humans↗

PubMed2026

One Year After a Cyberattack: Lessons Learned and Dosimetric Analysis of Contingency Radiotherapy Plans.

PURPOSE: Cyberattacks on health care institutions pose significant risks to patient care, particularly in radiotherapy departments, which are heavily reliant on digital systems. This study examines the impact of a ransomware attack on our hospital and evaluates the effectiveness of the contingency measures implemented to resume radiotherapy treatments. METHODS AND MATERIALS: Following the cyberattack, our radiotherapy department faced a complete shutdown. After an initial estimate considering a shutdown of several weeks, a contingency plan was executed, including manual patient data retrieval and collaboration with a backup hospital. Contingency plans were prepared and delivered within hours, despite a partial lack of information. These plans allowed some patients to restart treatment 3 days after the attack. A dosimetric analysis was performed for the contingency plans, including various pathologies, mainly glioblastoma, head and neck cancers, and lung cancer. We compared the original and contingency plans in terms of dose coverage to the clinical target volume, biological effective dose, and their clinical impact as assessed at the 1‑year follow‑up after the cyberattack. RESULTS: Treatments resumed within 12 days at our hospital. Patients with glioblastoma showed good target coverage because of generous margins, resulting in favorable outcomes. In head and neck cases, the lack of detailed imaging led to significant target volume misses, suggesting that more conservative initial treatments could have been beneficial. Lung cases demonstrated accurate peripheral lesion targeting but faced challenges in central lesions because of the absence of positron emission tomography information. In most cases, the approach of using a contingency plan, even with limited information, led to a higher biological effective dose than would have been achieved if treatment had been stopped until full recovery at our hospital. CONCLUSIONS: The study highlights the critical importance of robust contingency planning in radiotherapy departments, emphasizing the need for backup systems and tailored approaches based on tumor location and available diagnostic information. These lessons emphasize that preparedness for digital disruptions should not focus exclusively on information and technology infrastructure.

Humans↗

PubMed2026

Beyond predictive performance: A systematic review and critical methodological appraisal of AI/ML and conventional modelling strategies in breast, colorectal, and pancreatic Cancer.

BACKGROUND: Predictive modelling for cancer risk, treatment-related complications, and survival is central to precision oncology. Conventional logistic regression (LR) and Cox proportional hazards (CoxPH) regression remain widely used but are limited when modelling nonlinear interactions, high-dimensional imaging features, and multimodal clinical-metabolic predictors. Artificial intelligence (AI) and machine learning (ML) methods offer expanded capability through automated feature extraction, ensemble learning, and flexible survival modelling, but the evidence on when AI/ML adds value over conventional models across cancer sites and predictive tasks remains fragmented. OBJECTIVE: To systematically evaluate the methodological performance, validation strategies, and translational limitations of AI/ML models compared with conventional statistical models in published predictive-modelling studies for breast, colorectal, or pancreatic cancer. METHODS: PubMed, Scopus, and Web of Science were searched for studies published between January 2019 and March 2025. Two reviewers independently conducted title-and-abstract screening, full-text eligibility assessment, and PROBAST risk-of-bias assessment. Sixty-five studies (n = 907,567 participants) were narratively synthesised by cancer site, predictive task, model family, comparator, validation strategy, predictor modality, and calibration or explainability reporting. RESULTS: The 65 studies comprised breast cancer (n = 35), colorectal cancer (n = 21), and pancreatic cancer (n = 9). AI/ML superiority over LR and CoxPH was task- and data-dependent. CNN- and U-Net-based models predominated in imaging and body-composition tasks, tree-based ensembles consistently outperformed LR for tabular perioperative complication prediction, and CoxPH remained competitive, and in the largest pancreatic risk study, superior to XGBoost (C-index 0.802 vs 0.723) in well-structured datasets. PROBAST analysis-domain risk was moderate in 54 of 65 studies (83%), driven by limited external validation, sparse calibration reporting (11/65), and few decision-curve analyses (7/65). CONCLUSION: AI/ML adds the most methodological value in imaging-derived feature extraction and nonlinear perioperative prediction, while conventional regression remains preferable in large, structured datasets with linear predictors. Clinical translation requires standardised body-composition definitions, external validation, calibration assessment, decision-curve analysis, and explainability, in line with TRIPOD+AI and CLAIM standards.

Humans↗

PubMed2026

Association of cancer antigen 15-3 with distant recurrence in immunohistochemically defined breast cancer subtypes in Canadian Cancer Trials Group MA.32.

BACKGROUND: Circulating levels of cancer antigen (CA) 15-3 have been associated with distant breast cancer recurrence; data on breast cancer subtypes are sparse. We examined associations of CA 15-3 with outcomes across immunohistochemically defined breast cancer subtypes in MA.32. METHODS: A total of 3649 participants with T1-3, N0-1, M0 breast cancer were randomly assigned; 2740 (75.1%) provided blood at entry (mean = 278 days postdiagnosis) and 6 months later. Prognostic associations of baseline and 6-month change in CA 15-3 with distant recurrence-free survival (RFS) were examined in luminal (estrogen receptor-positive and/or progesterone receptor-positive, HER2-negative), triple-negative (estrogen receptor, progesterone receptor, HER2 negative) and HER2-positive (any estrogen receptor, progesterone receptor) breast cancer using Cox proportional hazards models. RESULTS: Mean age was 52 years. Breast cancer was luminal in 1589 (58.7%), triple negative in 655 (24.2%), and HER2 positive in 464 (17.1%) participants. Median follow-up was 96 months. CA 15-3 at study entry was not associated with outcome in any subtype. Rising CA 15-3 at 6 months was associated with poor distant RFS in luminal and triple-negative breast cancer (hazard ratio [HR] per 25% increase = 1.41, P < .0001, and HR = 1.35, P < .0001, respectively). New elevations in CA 15-3 at 6 months were adversely associated with distant RFS in those with luminal or triple-negative breast cancer (HR = 4.14, 95% CI = 2.69 to 6.38; P < .001; and HR = 3.57, 95% CI = 1.59 to 7.99; P = .002, respectively). In HER2-positive breast cancer, CA15-3 was not associated with distant RFS. CONCLUSION: Rising CA 15-3 was associated with reduced distant RFS in luminal and triple-negative breast cancer but not in HER2-positive breast cancer. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov NCT01101438.

Humans↗

PubMed2026

Cochlear Implantation in Sickle Cell Disease: A Systematic Review of Feasibility and Outcomes.

INTRODUCTION: Sickle cell disease (SCD) is associated with systemic complications, including sensorineural hearing loss (SNHL) from microvascular occlusion and chronic inflammation. Although reports link SCD to higher rates of SNHL, current evidence is limited by small sample size, varied audiologic methods, and lack of standardized screening. This systematic review summarizes available literature on SNHL and cochlear implantation (CI) in SCD. METHODS: A literature search of PubMed MEDLINE, Embase, Scopus, Web of Science, and CINAHL identified 79 citations. After removal of duplicates, 35 records were screened in Rayyan. Studies published between January 1, 2000, and June 30, 2025, were eligible if they reported patients with SCD who developed hearing loss and underwent CI. Nine full texts were reviewed, and 4 met the inclusion criteria. Screening and review were performed independently by 2 authors per PRISMA guidelines. RESULTS: Across 4 case reports, a total of 5 patients with SCD underwent CI, ranging in age from 2 to 42 years. Four presented with bilateral severe-to-profound SNHL and one with unilateral loss. Implantation was technically feasible in all cases, including patients with cochlear fibrosis or ossification requiring modified insertion techniques. Postoperative outcomes were favorable: all patients demonstrated reliable device function and low impedances. Only 60% showed meaningful auditory benefit, characterized by improved functional speech perception in 2 patients (40%) and access to the speech frequency range with hearing testing going from moderate/profound hearing loss to mild hearing loss in 3 patients (60%). Complications occurred in 2 patients (40%): one developed unilateral middle ear infection leading to meningitis, and another experienced a postoperative pulmonary embolism requiring anticoagulation. The remaining 3 patients (60%) had uncomplicated recoveries with reported improved hearing from moderate/profound hearing loss to mild hearing loss post implantation. CONCLUSION: While CI appears feasible in SCD, our findings suggest that additional data are needed to assess its effectiveness in this patient population. However, evidence is limited to case reports, and complications such as thromboembolism and rapid cochlear fibrosis highlight the need for close perioperative management. More comprehensive studies with larger sample size are required to define surgical risk, optimize management, and establish best practices for timely implantation in this population.

Humans↗

PubMed2026

Enhancing Self Care Among Oral Cancer Survivors Using a Digital Approach: The Empowered Survivor Trial.

BACKGROUND: Oral and oropharyngeal cancer survivors experience debilitating physical and psychosocial challenges. Little knowledge exists on the efficacy of interventions to enhance self-efficacy in managing these challenges, increase survivorship preparedness, and improve health-related quality of life (HRQoL). METHODS: Individuals (n = 643) diagnosed with oral or oropharyngeal cancer diagnosed within past 3 years were randomized to a digital intervention, Empowered Survivor (ES) or a Generic Online Intervention (GO). Primary (self-efficacy, preparedness, HRQoL) and secondary outcomes (self-care activities) were measured at Baseline, 2-months, and 6-months. RESULTS: Participants assigned to ES reported greater self-efficacy and increased self-care activities of oral self-exams, swallowing, and mobility exercises than those assigned to GO (self-efficacy: 2 months, p = 0.003, 6-months, p < 0.001; self-care activities). CONCLUSIONS: The ES enhanced self-efficacy and increased self-care activities. Further examinations of survivorship preparedness and HRQoL in oral and oropharyngeal cancer are warranted. TRIAL REGISTRATION: Registered on clinicaltrials. gov as NCT04713449.

Humans↗